This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A small pilot study was performed in Italy in participants with ALS. Sixteen participants were treated with 300 [unreadable]?? 450mg/day of lithium (target serum level 0.4-0.8 mEq/L) and riluzole;28 participants received only riluzole. Participants treated with lithium demonstrated a slower rate of functional decline as measured by the ALSFRS-R. The study was small and participants were not blinded to treatment. This is a double blind, randomized, placebo-controlled clinical trial evaluating the safety and efficacy of lithium and riluzole compared to placebo and riluzole. Approximately 250 volunteers will be recruited from multiple centers in the US and Canada that are part of the Northeast ALS Consortium (NEALS) and the Canadian ALS Clinical Trials and Research Network (CALS). The primary outcome measure is disease progression defined as the time to decline of 6 points in the ALSFRS-R scale or death. The ALSFRS-R will be administered at the Baseline Visit;this will be considered the baseline score for each participant. A drop of 6 points or more in the ALSFRS-R will be defined as disease progression and treatment failure. Participants will then be treated with lithium for the period of the study (up to 52 weeks total). Study site staff will remain blinded to initial group assignments and will remain blinded to the total ALSFRS-R scores and be unaware of the date when a participant is switched from placebo to lithium.